Ninety percent (90%) of bladder cancers are transitional cell carcinomas which are superficial at early stage but later become invasive. Surgical removal is possible but a high rate of recurrence is experienced. Surgical removal is therefore often followed by further treatment, either to prevent recurrence or to inhibit the growth of tumor cells that were not surgically removed. Various agents are employed, administered by instillation into the bladder (intravesicular instillation). Adverse reactions and toxic effects often limit the duration of treatment and prevent commencement of treatment until several weeks after surgery.
Reports on the use of dextran sulfate as an inhibitor of tumor cell growth are rare. U.S. Pat. No. 5,055,301 to Voigt et al discloses inhibition of both androgen-dependent and androgen independent prostate carcinoma cells in culture. In vivo data were not reported. Imagawa, A. et al., (1980) Gan Kagakuryoho 7:127-131, reported that a combination of carboquone, cytarabine and dextran sulphate instilled into the bladder of post-operative bladder cancer patients yielded no recurrences in 21 patients. Previous studies have shown that polyanionic drugs such as Suramin also inhibit binding of growth factors to their receptors and inhibit cell proliferation [Gansler, T. et al. (1992) J. Urol. 148:910; Pollack, M. et al. (1990) J. Natl. Cancer Inst. 82: 1349; Coffey, R. J. Jr., et al. (1987) 132: 143-148]. On the other hand, Sorimachi, K. et al., (1992) Cell Biol. Int. Rep. 16: 63-72, failed to observe an inhibitory effect of dextran sulfate or other polyanionic compounds on the growth of human urinary bladder carcinoma cells in culture. It has been shown that the in vitro inhibition of T24 and HT1376 transitional cell carcinoma cell line proliferation by Suramin results from specific inhibition of epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) binding (Gansler, supra). The in-vivo action of Suramin was demonstrated by documenting intravesical inhibition of MNU induced bladder tumors in Fisher 344 rats [Graham, S. D. Jr., et al. (1995) J. Urology 45(1): 59-63]. Dextran sulfate is also a polyanionic compound which, like Suramin, has minimal toxicity and can safely be administered intravenously [Smith K. et al. (1989) Cancer Res. 49(21): 5810-5815].